Numerous disturbances or disorders of the eye lead to an increase in intraocular pressure (IOP). For example, post-surgical or post-laser trabeculectomy, ocular hypertensive episodes and glaucoma all can result in increased IOP.
On the basis of its etiology, glaucoma has been classified as primary or secondary. Primary glaucoma, also known as congenital glaucoma, can occur in the absence of other ocular conditions. The underlying causes of primary glaucoma are not known. It is known, however, that the increased IOP observed in primary glaucoma is due to the obstruction of aqueous humor flow out of the eye. In chronic open-angle primary glaucoma, the anterior chamber and its anatomic structures appear normal, but drainage of the aqueous humor is impeded. In acute or chronic angle-closure primary glaucoma, the anterior chamber is shallow, the filtration angle is narrowed, and the iris may obstruct the trabecular meshwork at the entrance of the canal of Schlemm. Dilation of the pupil may also push the root of the iris forward against the angle to produce pupillary block precipitating an acute attack. Additionally, eyes with narrow anterior chamber angles are predisposed to acute angle-closure glaucoma attacks of various degrees of severity.
Secondary glaucoma results from another pre-existing ocular disease such as, without limitation, uveitis, intraocular tumor, enlarged cataract, central retinal vein occlusion, trauma to the eye, operative procedures and intraocular hemorrhage. Accordingly, any interference with the outward flow of aqueous humor from the posterior chamber into the anterior chamber and subsequently, into the canal of Schlemm can lead to secondary glaucoma.
Considering all types of glaucoma together, this ocular disorder occurs in about 2% of all persons over the age of 40. Unfortunately, glaucoma can be asymptomatic for years before progressing to a rapid loss of vision.
In cases where surgery is not indicated, topical β-adrenoreceptor antagonists have traditionally been the drugs of choice for treating glaucoma. Certain eicosanoids and their derivatives have also been reported to possess ocular hypotensive activity, and have been recommended for use in glaucoma management. Eicosanoids and their derivatives include numerous biologically important compounds such as prostaglandins and their derivatives. While prostaglandins were earlier regarded as potent ocular hypertensives, evidence has accumulated that some prostaglandins are highly effective ocular hypotensive agents ideally suited for long-term medical management of glaucoma.
Prostaglandins can be described as derivatives of prostanoic acid which have the structural formula:
Particularly useful hypotensive prostaglandins include PGF2α, PGF1α, PGE2α, and certain lipid-soluble esters, such as C1 to C5 alkyl esters, e.g. 1-isopropyl ester, of such compounds. Many patients needing to lower their intraocular pressure are on fixed combination therapies such as COMBIGAN® and GANFORT®. However, for some patients, combination therapies are not enough to lower intraocular pressure and Triple Combination therapy is required. The combined effect is expected to result potentially in additional IOP reduction in patients with chronic open-angle glaucoma or ocular hypertension who are not well controlled on 2 IOP-lowering agents.